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Hopefully they define their "mean" survival numbers better than their definitions for response rates
for the record, i think antibodies with conjugated isotopes are a pain in the ass... you need specially competent people and facilities to administer.
t301 and 302... those are the only 2 phase III trials that i am aware of. Looks like 301 is the one with overall survival as an endpoint, and started in 2000. That's coming up to 5 years now.
Officially they are not complete. Because they're filing for accelerated approval, either the company has no intention of finishing it, or it has failed.
MY concern with Introgen is simple.
Survival data is the strongest type of data for cancer trials. INGN has a phase III that measured survival.
If the phase III was successful in improving survival, surely they would use it as the pivotal trial and not go through the accelerated approval route using surrogates of survival. If the phase III wasn't successful and they're trying to apply based on surrogates, won't the FDA see that their surrogate endpoints were not validated by improved survival?
I read, but initially did not believe, a post on yahoo about the company having over 1 PR per week over the last year. So I checked up on it and it's true... that's a lot of publicity for a scant amount of data. A bit of a red flag for me as well.
>The investor who wishes to max out the time spans yielding the highest return must consider other variables <
I wholly agree, and freely admit that such breadth vis-a-vis trading is beyond my scope.
Luckily I have another day job to fill in the missing gains
good luck!
Sentiment is your thing
I'm not an efficient trader by any means. I tend to try and trade stocks that I think have a strong fundamentals... that gives me the piece of mind that the bottom won't fall out unexpectedly during a trade.
I think that objective responses can be reliable markers of survival provided that they are high enough. So in that YMI example, if you're doubling objective responses to well north of 70%, then it is reasonable, in my opinion, to speculate on a survival benefit.
On the contrary, I don't think a 10-15% objective response rate as a monotherapy is a reliable indicator of a survival benefit.
I prefer to be a little more conservative. Everyone has their own area of comfort.
good luck!
"Can you please favor me with a reply regarding the major disticntion between surrogate endpoints ( aka:putative objective data?) and survival data (I removed long term)."
Surrogate endpoints were initially expected to be early indicators of an eventual survival benefit. However, the relationship has not been a simple one in oncology. In oncology trials, companies often look at tumour shrinkage (response rate) as a surrogate. However, an increase in response rate has not always translated into a survival benefit. Therefore, response rate is becoming a tough sell with the FDA, in my opinion.
As an investor, the major distinction is best exemplified by Iressa versus Tarceva. Nuff said.
It also presents itself, to some degree, in the general "perception" of Avastin versus Erbitux. In my opinion, Erbitux still has a bit of a weight on its shoulders from not having shown a survival benefit. Because of that, it will always be running against big brother (avastin, with survival benefit) trying to catch up.
The possible scenario developing for head and neck cancer with erbitux versus INGN's p53 adenovector may well resemble Avastin vs. Erbitux in colorectal cancer.
When survival data comes out, it's not a great position to be holding the competitor's (surrogate) bag.
Fundamentally, I wouldn't touch INGN with a 100 foot pole. I think they're trying to hide a phase III trial failure.
Doesn't mean you can't trade it. It appears to me to have a strong retail following which guarantees that you'll get good price swings.
Any opinion as to why YMI is changing the patient population for the "pivotal" form of this trial? I would think that the strongest position would be to resume testing in the last-ditch population (build on the strong results) rather than moving up into a less-advanced stage using combination therapy.
First rule of any scientific endeavour is to test the null hypothesis. The FDA also uses the null hypothesis. As it relates to biotechs, there are two versions of it that go hand in hand:
1) a drug X for a condition Y at a dosage Z is not safe until proven otherwise.
2) a drug X for a condition Y at a dosage Z is not efficacious until proven otherwise.
Objective data is required to address the two hypotheses. Without data, it is merely a hunch or a gut feeling. Nothing wrong with that, but it doesn't get drug approvals or address safety and efficacy concerns.
I admit that I don't see how CJC's product can not be outcompeted or outperformed by HGSI's albugon.
Albugon is simply a better controlled formulation of cjc's drug. Removing the variability that is inherent in the in vivo coupling that cjc requires is a big plus in my book. My bet is that over the long term, you get much more consistent results with albugon.
To my knowledge, the phase II for Myriad is focusing on mental acuity. I've not read that they are physically measuring amyloid levels.
congrats!
That's a triple and a double in consecutive years... a 6 bagger.
very nice
yeah, i'll need to listen to that before i clutter up the board any more.
From that transcript, it sounds like Gold is on drugs. First he says that, unlike 9901, 9902A did not show a statistical benefit for gleason less than 7. But in the next sentence he claimes that what they're seeing is encouraging?!
Presumably his spin is that since 9902A is trending similarly to 9901, and since the latter was positive, it bodes well for the former.
>How reasonable is it to conclude that Provenge confers a survival advantage regardless of Gleason score, and the retrospective analysis picked up a chance grouping in TTP?<
I don't think it would be unreasonable to consider that a specific subgroup in a trial, provided it was large enough, could be the main driver for an overall survival benefit. So a specific subgroup with a lengthened TTP consequently stretches out median survival in the trial and allows it to reach significance.
(sorry, i had to edit this: Since you refered specifically to Provenge, I have to say that it doesn't look very reasonable to assume that a broad survival advantage is offered by Provenge. I initially read your questions more as asking "is it reasonable to think that an ITT survival advantage could be observed with only a subgroup showing an improvement in TTP?" Clearly I got it all wrong.)
I think this ambiguous situation with DNDN and its 9901 and 9902A trial results are the exact reason why the FDA likes randomized trials with prospectively defined endpoints
Let's see if i have this straight:
For 9901, the 7 or less gleason subgroup showed TTDP and eventual survival improvement.
In 9902A, the 7 or less gleason subgroup showed neither TTDP or survival improvement.
Is this correct?
yeah, you're right.
I want one of these cases to go before ODAC so I can see what happens.
Maybe i'll listen to their jpm presentation. I wasn't planning to at first.
I don't disagree with you about the underpowered nature of the trial. In fact, it would have been to the company's advantage to come out and say so. But they obviously tried to play games with the PR of this trial, and the market is punishing them for it.
I would think this is a buying opportunity for DNDN bulls, provided that they call the company and voice their displeasure so that the lesson is learned
I wouldn't worry if overall survival is the primary or secondary endpoint. As long as it is a prospectively defined endpoint and the arms are well balanced through randomization, the results should be valid.
But I hate Dendreon's use of the word "similar" in the press release. Whereas they note that TTDP did not show a stat sig difference, they claim the survival compared to placebo is "similar" to the 9901 trial. But what the heck does that mean? A human and an elephant are similar if you consider that both are mammals. If I remember correctly, 9901 1) failed the ITT analysis at first but showed a subgroup survival benefit; but 2) over time, the ITT analysis become significant. So are we similar to 1 or 2?
Without clarification, it is hard not to conclude that the survival analysis failed to meet statistical significance despite their dancing around this point. And for a trial with 98 total patients, it is reasonable to accept that the trial was simply underpowered to show a statistically significant benefit. An honest PR would have been the best and most reasonable policy in this case.
re: supercharging dendritic cells:
I have no specific comment on the SOCS1 protein that the researchers have focused on.
I do like the fact that they're doing the RNA interference ex vivo since you're more apt to have very high efficiencies for the intended transformation. It is much more preferable than trying to intervene by RNA interference in a systemic manner.
Sorry that i have no insight on SOCS1.
LMAO!
Damn i can be such a dope sometimes.
Thanks for the laugh. I'll close all those google searches now.
bastard
I've honestly not heard of deferred accelerated approval. Had no luck digging anything up from FDA site. Have a link handy?
On the surface, the concept doesn't seem like it would fly in the marketplace if / when the phase III misses its survival endpoint. The drug would become iressa would it not? Being marketed with the spectre of a failed survival trial over its head. Thoughts?
As we know, prospectively defined endpoints are much better than retrospective musings
For 2005, I'll be holding or looking to add:
osip, imcl, gnvc, telk, ctic, mlnm, gtcb, mygn, arql, acad, medx, eln, exel
Haven't decided what to do with celg yet. I sold it late in the year and will probably sit on the sidelines until the revlimid situation sorts itself out.
I neglected to mention that my biggest percentage winner was eln. However, I had such a small position that it didn't really make much of a dent in the overall picture. Sad...
I'm getting curious about INGN. Something isn't right there. It's my early bet for "Disaster of 2005".
>My question is... with all the day traders and momentum traders looking for events like PARS failure, wouldn't it be a good idea for a previously long investor to:
A) Hold any shares you want to sell until the bounce.
B) Pick up some extra shares on D-Day, then hold for a few days and sell on the bounce to make up a little of the loss from your long shares.<
I interpret your choices as a question of how to trade. I'm not a good trader, so I wouldn't know if or when a bounce is coming, or how big a bounce, etc...
My perspective is that if a biotech has a failed pivotal trial or failed an NDA, then i don't want to be owning its shares, period. So buying after failure is not an option in my book. And guessing about the timing and magnitude of a post-failure bounce is beyond my abilities. But if you consider that most large failures result in a 60% decrease in stock price, is a risky, post-failure trading strategy to recoup 10% of those losses really worth it? In other words, if you're holding a stock that crashes from 10 to 4 dollars per share, is it really worth the additional risk to the downside in order to possibly exit at 5 dollars a share? Up to you, but for me it isn't.
To color my comments, my personal investment account only has biotechs in it. So interpret my comments accordingly.
>I really appreciate the candor of those willing to share their successes, failures, luck, and foolishness--a good way to learn. <
My experience as an individual investor is that you have to work overtime to avoid the BIG loss. That means staying away from companies where you feel disclosure is very shady, and making sure that you head into the "binary" events with a solid game plan. Puts as insurance are invaluable, in my opinion. Not only can they save you some $$$, they allow peace of mind.
Someone asked earlier how to exit a position where a pivotal event turned negative. From watching some of the colossal flops (and participating in one), the best thing to do in my opinion is sell out right away if a pivotal trial misses it's primary endpoint or an NDA gets rejected. There is usually a bit of a small bounce about 3-4 days after the initial big drop which some desperately interpret as a sign of recovery. That is rarely the case, and a slow but steady decline in share price ensues. You're better off having sold in premarket or by 10 am on the day. As with anything, there are exceptions; but in general, this strategy holds.
Set your calendars.
Second line median survival in ovarian cancer is about 9 months, so at a minimum, the control arm for ASSIST-1 may have a median survival of 9 months max. So Q4 for results. The full enrollment of ASSIST-1 also confirms Prudential's Zhang as nothing but a useless mouthpiece analyst.
The company presses on for ASSIST-2 in 3rd line NSCLC against Iressa despite recent results.
And finally, their third ASSIST trial is up and running but with no SPA. From hearing the company talk, I suspect that this was done for two reasons:
- to speed up the start date of the trial (no time spend negotiating SPA)
- company thinks that the results will be a no-brainer.
Earlier, they had mentioned that the primary endpoint will be objective response rate. They previously stated that the trial will end once everyone has received their full treatment and been monitored for an objective response. I suspect that once the objective response data is available (prob late Q3, early Q4), only the PFS data will be mature. I find it unlikely that the overall survival data will be mature by q4. We'll see if their decision to ignore an SPA for this trial costs them in the long run.
Telik Completes Enrollment in ASSIST-1, Initiates ASSIST-3 and Reviews Status of ASSIST-2 Clinical Trials
PALO ALTO, Calif., Dec. 29 /PRNewswire-FirstCall/ -- Telik, Inc. (Nasdaq: TELK - News) announced the completion of enrollment for the ASSIST-1 clinical trial of TELCYTA(TM) (TLK286), and the initiation of a new randomized Phase 3 trial of TELCYTA called ASSIST-3, in second line platinum refractory or resistant ovarian cancer.
ASSIST-1 is a randomized Phase 3 study designed to enroll 440 women in the third line treatment of platinum refractory or resistant ovarian cancer. Enrollment is complete.
ASSIST-3 is a randomized Phase 3 study designed to enroll 244 women with 122 to be treated with the combination of TELCYTA plus carboplatin, and 122 to be treated with Doxil®. The trial endpoints are objective response rate, progression-free survival and overall survival. The study is based on a positive multicenter Phase 2 study of the combination of TELCYTA plus carboplatin in platinum refractory or resistant ovarian cancer, first presented at the annual meeting of the American Society of Clinical Oncology earlier this year and later updated at the Tenth Biennial International Gynecologic Cancer Society meeting. The initial participating institutions are the Harvard Affiliated Hospitals including the Massachusetts General Hospital, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center.
ASSIST-2 is a randomized Phase 3 study designed to enroll 520 patients in the third line treatment of platinum resistant non-small cell lung cancer. Enrollment continues as planned and the company anticipates completion of enrollment in the first quarter of 2005.
TELCYTA is a small molecule drug candidate designed to be activated by GST P1-1, an enzyme present in cancer cells. Upon activation, an intracellular process known as apoptosis, or programmed cell death, occurs. TELCYTA was discovered through the application of Telik's proprietary drug discovery technology, TRAP. TELCYTA has been successfully tested alone and in combination with approved cancer drugs in Phase 2 clinical trials in ovarian, non-small cell lung, breast and colorectal cancer.
Patients and caregivers may receive more information about ASSIST-3 by calling 866-485-5286. For information on ASSIST-2, visit www.assist-2trial.com; for ASSIST-1, visit www.assist-1trial.com.
So so year... about 15% increase.
Your post made me look at my transactions over the past year. It appears to have been mostly an accumulation year, with, percentage-wise, a couple of large gains (osip / gnvc) and a large paper loss (gnvc). 2005 is shaping up to be generally an accumulation year once again, with ctic, gtcb and telk presenting the potential large gains or losses.
> I'll be keeping a close watch in case the AD outcome is a bust. <
That's a good point. For those interested in the stock but leery of its recent large run, weakness following an AD bust would be a great opportunity. I would personall look to increase if that were the case.
Sounds like my ctic strategy... guess i fear commitment
i was thinking more about imgn's internal capability to design and execute a successful clinical trial. At least i should give them credit because they've realized their weakness and stayed away from it.
I follow MYGN. Luckily, they've had a nice run this year.
The company is receiving revenues from a breast cancer diagnostic test. They are attempting to expand their presence in the "predictive medicine" arena, and today's announcement is along that line. In the clinic, they have an enantiomer of flurbiprofen for alzheimer's disease. Because of my lack of knowledge in the CNS area, I have no substantive comments on this drug's chances, or lack thereof.
If their revenues and expenses stay flat, they have about 3 years of money in the bank.
As for IMGN, i think it is a good short. This company is being used as a retirement vehicle for the CEO, and he has lost all motivation to advance the company independently. He's sold out all his pipeline, and makes these collaborations in an attempt to hopefully get one drug on the market and draw royalties. There is no explosive upside to this company, and I'm convinced that their acumen in the clinic is next to nil.
Sometimes these CEOs are too transparent... even novices like myself can see through them.
Cell Therapeutics, Inc. Announces $18.4 Million Direct Equity Placement
SEATTLE, Dec. 20 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC; Nuovo Mercato) announced today that it has agreed to sell approximately 2,586,000 shares of its common stock to several institutional investors in a registered direct offering at a negotiated price per share of $7.10.
The shares of common stock in this offering are being issued under an existing shelf registration statement on Form S-3, which was declared effective by the Securities and Exchange Commission on March 22, 2004. A prospectus supplement related to the offering will be filed with the U.S. Securities Exchange Commission. Copies of the prospectus supplement may be obtained directly from Cell Therapeutics, Inc., 501 Elliott Avenue West, Suite 400, Seattle, Washington 98119, Attention: Investor Relations.
This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
I realize that these are large trials that, by their sheer size, likely balance the arms evenly for multiple factors.
However, with cardiovascular disease being a very multi-modality disease with a great heterogeneity, I'm not convinced that one could properly assess true cardiovascular risk in these trials without prospectively balancing the arms based on cardiovascular risk factors.
It would be sad if Celebrex was also pulled off the market. I think the true risks to the population at large are being exaggerated. I place the odds of Celebrex staying on the market at 95%. 5% chance of it being removed because I fear the irrational judgment of the masses,
erniewerner is great! eom.
I wonder if these polyposis patients present a greater CV risk consequent to COX-2 inhibition?
It was the polyposis population that did Vioxx in as well.
>I wonder if they should think about cherry picking iressa reps? <
Man i hope not. Of all the reps that I see in cardiology, the AZN ones are the most pushy and annoying. If the onc reps are like that as well, some oncs may be happy to prescribe Tarceva just to get the AZN reps off their backs
I agree in general.
I'm just wondering if the monitoring board saw a significant risk in the blended population (400 & 800 mg dose) and stopped things until it could figure out exactly what was going on. So it could still "technically" be one of the dose groups disproportionately accounting for the observations in the blended population.
The one implication to that line of reasoning is that the risk in the 800 mg population is an even higher percentage than indicated in the blended analysis.
I concur with you regarding the potential impact of this data 400 / 800 mg data when one considers the typical dose used in the main revenue driving population.
Feel bad for these FAP patients. It's been clear that Celebrex was never working through a COX-2 mechanism in this population. So basically they were being overdosed for a unique cross-reaction / side effect of celebrex that, for reasons unknown, shrank their intestinal polyps. Moral of this story: don't take high doses of a drug in a disease setting where its mechanism of action has been invalidated.
Also nice to see that the median survival of tarceva at 6.7 months blew out Iressa's median survival of 5.6 months. I realize it's only one point on a curve, but this ISEL Data appears to be an unambiguous win for Tarceva in all aspects.
damn!
I was going to post the same thing about a price increase. I wouldn't be surprised at all if Tarceva gets a little more expensive after a month on the market.
The AZN reps have absolutely nothing to go on. I hope / suspect that the cannabilization of Iressa sales by Tarceva will look much like what we see when generics hit the market.
I haven't listened to the AZN CC, but i'm happy that smokers were mentioned. Nothing like having some of my scientific mumbo-jumbo validated in big trials.
Finally, this is probably one of the few times when one can cheer for the failure of a cancer drug trial. Tarceva-lite will probably die a quick death.
Telik getting hit today because one of their pivotal trials is now basically against a dead-drug. The SPA will help a little bit in protecting the ASSIST-2 trial from complete irrelevancy. Ovarian cancer is still the most likely indication for marketing approval of Telcyta, since the salvage setting monotherapy NSCLC data was relatively weaker.
As for PFE, I'm wondering if the problems are in the 800 mg group since the SAP trial with 400 and 800 mg had problems, but the SAP with 400 mg only didn't. If so, this is a non-event for the main revenue driving joint pain population. I don't think a many patients are on a continual 800 mg daily regimen.
Ok, now to gloat on the IMCL board...
>Makes you wonder if CTIC has an in-house general counsel. Those comments will be a magnet for the class-action bloodsuckers if there is a major sell-off following the data reporting.<
Exactly. All the class action lawyers will need to do is pull up the title of yesterday's pr.
sad.
CTIC:
Case in point of Bianco talking up the results is this morning's PR.
Dumb, in my opinion.
re: ctic
This whole game of updating the events at monthly intervals is getting me annoyed.
You can't solve anything from the blended data that they're reporting, so it's really a way for CTIC to juice up the *ahem* naive investors. (I use that term with hesitation since, in the stock market, naive is relative.)
The skeptic in me is thinking that Bianco is milking the "longer than expected blended median survival" to increase share price and put forward another offering.
A success in Stellar 3 will boost the share price. However, they really need to follow it up with an additional success in Stellar 2 or 4. Otherwise, the market will pummel them somewhat post-approval (a la OSIP) because the on-label population will be restricted to begin with.